The pathogenesis of AIDS-dementia complex (AIDS-DC) is poorly understood. Its relationship to the human immunodeficiency virus (HIV) is particularly perplexing. We suggest that if HIV and the damage to brain are directly related, neuropathological changes in AIDS DC should co-localize with HIV regionally and cytologically. We therefore propose to delineate morphometrically the specific components(s) in the central nervous system (CNS) which are damaged in AIDS-DC; and to compare brain maps of damage and of HIV distribution (by in situ nucleic acid probe hybridization (ISH) and immunocytochemistry (ICC)) in a series of postmortem human AIDS brains. Other HIV-related markers will also be mapped: 1) the CD4 surface receptor (ISH and ICC), recently shown to be present in normal brain and 2) the HLA-DR major histocompatibility marker (ICC), recently shown to be inducible in astrocytes (and possibly CNS endothelium) as a component of stimulated antigen processing by these cells. These various phenomena, if colocalized with specific CNS damage or HIV infection, might represent markers which explain HIV-neurotropism and support a direct role for HIV in the injury to specific CNS components in AIDS-DC.